Twenty years of the French Renal Epidemiology and Information Network.

Background: The French Renal Epidemiology and Information Network (REIN) is 20 years old. It is not just a national data registry, but rather an epidemiological and informational network serving patients with chronic kidney disease, nephrology teams and health services. Methods: The past 10-year trends of the incidence and prevalence of renal replacement therapy by dialysis or kidney transplantation and waitlist activity are presented. To detect potential significant changes in trends from 2012 and 2021, a Joinpoint regression model was used. Results: The overall incidence of treated end-stage kidney disease (ESKD) was 169 per million population (pmp) in 2021. It was stable despite an increase in the incidence of diabetes. We found a decreasing trend in the proportion of patients starting dialysis in an emergency but an increase in those starting haemodialysis (HD) with a temporary catheter. Peritoneal dialysis decreased by 1.7% each year, whereas home HD, although involving only 1% of dialysis patients, increased by 10% each year. For patients not treated at home, the median time to drive from the patient's home to the dialysis unit was 17 min. The proportion of patients on the transplantation waitlist at the start of dialysis increased from 7% to 12%. Among the 111 263 new ESKD patients from 2012 to 2021, 8% received a first transplant at 1 year and 20% at 5 years. Among kidney transplant recipients, the mean time on the waitlist increased from 13.8 to 22.6 months. Living donor transplants increased in frequency, representing 15% of kidney transplants. Conclusions: Data from the REIN registry allow for the evaluation of needs and provide a planning tool for French authorities. The progressive implementation of automatic data retrieval from dialysis informatics charts might alleviate the burden of data collection. Furthermore, the research activity the REIN engenders, resulting in renewed confidence by health authorities in the dynamism of French nephrology, allows for an optimistic outlook for the REIN.

Incidence of End Stage Kidney Disease and context of dialysis initiation / Incidence de la maladie rénale chronique stade 5 traitée par suppléance et contexte d'initiation de la dialyse

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of ESKD incidence, the following key messages were retained. Thanks to several studies conducted using data from the REIN registry, the spatial variations of incidence of stage 5 chronic kidney disease in the replacement stage could be explained, in part, by the health condition of the general population as well as by the socio-economic context and differences in practices. Just like what is observed in other countries, the incidence is stabilising, or even decreasing, especially among people who do not have diabetes. Thanks to the registry having provided an indicator on the initiation of the dialysis, a decrease in the rate of initiation of emergency dialysis (i.e., initiated less than 24 hours after a nephrology evaluation considering a vital risk for the patient) has been observed, resulting from an effort to understand and better anticipate the starting of the replacement.

À l'occasion des 20 ans du REIN (Réseau Epidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question de l'incidence de la maladie rénale chronique stade 5, les messages clés suivants ont été retenus. Grâce à plusieurs études menées à partir des données du registre REIN, les variations spatiales d'incidence de la maladie rénale chronique stade 5 au stade de la suppléance ont pu être expliquées, en partie, par l'état de santé de la population générale mais aussi par le contexte socioéconomique et des différences de pratiques. À l'image de ce qui est observé dans d'autres pays, l'incidence est en voie de stabilisation, voire à la baisse, en particulier chez les personnes non diabétiques. Grâce à la mise à disposition par le registre d'un indicateur sur l'initiation de la dialyse, on observe une diminution du taux d'initiation de la dialyse en urgence (c'est-à-dire initiée moins de 24 heures après une évaluation néphrologique considérant un risque vital pour le patient) résultant d'un effort pour comprendre et mieux anticiper le démarrage de la suppléance. L'initiation de la dialyse sur cathéter, autre indicateur de la prise en charge, n'a pour l'instant pas diminué mais avec la mise en place du forfait MRC en octobre 2019 et à distance de la pandémie, la préparation à l'épuration extrarénale devrait être mieux anticipée.

REIN: a tool to evaluate pratices / REIN : un outil au service de l'évaluation des pratiques

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of its role in practices evaluation, the following key messages were retained. The evaluation of our practices allows improving them as proposed by the concept of the Edward Deming wheel (Plan, Do, Check, Act). Measurement also allows setting goals and targets. Where there are recommendations available, the REIN indicators allow comparison with the identified targets. The REIN registry is an interesting tool to observe the deployment and impact of the recommendations in dialysis units and to evaluate the professional practices taking into account the patients' characteristics and the changes in the recommendations. Finally, the treatment indicators analysed using REIN data show the great diversity of practices from one region to another, the result of habits, training of nephrologists, the history of the care offered and sometimes the geography of the region and its population.

À l'occasion des 20 ans du REIN (Réseau Épidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question de REIN comme outil pour l'évaluation des pratiques, les messages clés suivants ont été retenus. L'évaluation de nos pratiques permet de les améliorer comme proposé par le concept de la roue d'Edward Deming (Plan, Do, Check, Act). Se mesurer permet également de fixer des objectifs et des cibles. Lorsque des recommandations sont disponibles, les indicateurs REIN permettent de se comparer aux cibles identifiées. Le registre REIN est un outil intéressant pour observer le déploiement et l'impact des recommandations dans les unités de dialyse et évaluer les pratiques professionnelles en tenant compte des caractéristiques des patients et de l'évolution des recommandations. Enfin, les indicateurs de prise en charge analysés à l'aide des données REIN montrent la grande diversité des pratiques d'une région à l'autre, fruit des habitudes, de la formation des néphrologues, de l'historique de l'offre de soins et parfois de la géographie de la région et de sa population.

Switch from Hemodialysis to Peritoneal Dialysis: Does the Time Spent on Hemodialysis Impact Outcomes in Peritoneal Dialysis?

INTRODUCTION: Switch from hemodialysis (HD) to peritoneal dialysis (PD) is unfrequent, but incentive strategies to perform PD can lead to an increase of these transitions. However, data on transitioning from HD to PD are scarce. We hypothesized that time spent on HD before transfer to PD would impact PD outcomes. METHODS: This registry-based, nationwide study analyzed patients transferred from HD to PD. Patients who began HD between January 2008 and December 2016 were included. Cox and Fine and Gray regression models were used to explore the relationship between time spent on HD before PD and outcomes in PD: PD cessation for death or retransfer to HD (composite endpoint); for death; and for retransfer to HD. RESULTS: Over the study period, 1,985 of the 77,587 HD starters (3%) were transferred to PD. The median time spent on HD before transfer to PD was 1.94 months (interquartile range [IQR] 1.02-4.01). The median survival time on PD after this transition was 20 months (IQR 18-21). Time spent on HD before PD was associated with increased risk of death or retransfer to HD (cause-specific hazard ratio [cs-HR] 1.01, 95% confidence interval [CI]: 1-1.02 for a 1-month increase) and death (cs-HR 1.02, 95% CI: 1.01-1.03) but not with retransfer to HD censored on death (cs-HR 1.00, 95% CI: 0.99-1.01). The results were similar when considering competing events. DISCUSSION/CONCLUSION: Switch from HD to PD is rare in France. Time spent on HD before transfer is associated with patient survival but not with retransfer to HD.

[Prevalence of iron deficiency in patients with non-dialysis chronic kidney disease: The CARENFER national, multicentre, observational study]. / Prévalence de la carence martiale dans une population de patients insuffisants rénaux chroniques non dialysés : étude nationale multicentrique observationnelle CARENFER.

INTRODUCTION: Iron deficiency is common and associated with worse outcomes in patients with non-dialysis chronic kidney disease. We performed a national, multicentre, observational and transversal study to assess the prevalence of iron deficiency as well as current iron deficiency screening practices in this population. PATIENTS AND METHODS: A total of 25 nephrology centres in France participated in the study. All adult non-dialysis chronic kidney disease patients who met the inclusion (GFR>15mL/min/1.73m2) and exclusion criteria and provided consent were systematically recruited over a 4-week inclusion period. Investigators were asked to perform a blood test (hemoglobin concentration, serum iron, serum ferritin and transferrin saturation) and to complete a questionnaire about their iron status monitoring practices. The primary objective was to assess the prevalence of iron deficiency (serum ferritin<100µg/L and/or transferrin saturation<20%). Secondary objectives were to evaluate the prevalence of absolute iron deficiency (serum ferritin<100µg/L and transferrin saturation<20%) and functional iron deficiency (serum ferritin≥100µg/L and transferrin saturation<20%), the prevalence of iron deficiency according to haemoglobin concentration and chronic kidney disease stage, the proportion of centres that perform routine evaluation of iron status and the number of patients receiving iron supplementation. RESULTS: A total of 1211 patients with non-dialysis chronic kidney disease were included in the analysis. The overall prevalence of iron deficiency was 47.1%. The rates of absolute iron deficiency and functional iron deficiency and anaemia were 13.4% and 17.1%, respectively. Among the 25 participating centres, 12 reported routine assessment of iron status in non-dialysis chronic kidney disease patients. CONCLUSION: In this observational study, a high prevalence of iron deficiency was observed among non-dialysis chronic kidney disease patients. Less than half of participating centres reported routine assessment of iron status.

Effect of emergency start and central venous catheter on outcomes in incident hemodialysis patients: a prospective observational cohort.

BACKGROUND: Unfavorable conditions at hemodialysis inception reduce the survival rate. However, the relative contribution to outcomes of predialysis follow-up, symptoms, emergency start or central venous catheter (CVC) is unknown. METHODS: We analyzed the determinants of survival according to dialysis initiation conditions in the nationwide REIN registry, using two methods based either on clinical classification or data mining. We divided patients into four groups according to dialysis initiation (emergency vs planned, symptoms or not, previous follow-up). "Followed planned starters" began dialysis as outpatients and with an arteriovenous fistula (AVF). "Followed symptomatic non-urgent starters" were patients who started earlier because of any non-urgent symptomatic event. "Followed urgent starters" had seen a nephrologist before inception but started dialysis in an emergency condition. "Unknown urgent starters" were patients without any follow-up and who had a CVC at inception. RESULTS: "Followed urgent" starters had the lowest 2-year survival rate (66.8%) compared to "followed planned" (77.3%), "followed symptomatic non urgent" (79.2%), and "unknown urgent" (71.7%). Compared to other groups, the risk of mortality was lower in followed symptomatic non urgent (HR 0.86 95% CI 0.75-0.99) and higher in followed urgent starters (HR 1.05 (95% CI 0.94-1.18). In data mining Classification And Regression Tree regrouping in five categories, the lowest 2-year survival (52.3%) was in over 70-year-old starters with a CVC. The survival was 93.2% in under 57-year-old patients without active cancer, 82.5% in 57-70-year-old individuals without cancer, 72.4% in over 70-year-old patients without CVC and 61.4% in under 70-year-old subjects with cancer. The hazard ratio of data mining categories varied between 2.12 (95% CI 1.73-2.60) in 57-70-year-old subjects without cancer and 4.42 (95% CI 3.64-5.37) in over 70-year-old patients with CVC. Therefore, regrouping incident patients into five data mining categories, identified by age, cancer, and CVC use, could discriminate the 2-year survival in patients starting hemodialysis. CONCLUSIONS: Although each classification captured different prognosis information, both analyses showed that starting hemodialysis on a CVC has more dramatic outcomes than emergency start per se.

Skeletal Muscle Index as a Prognostic Marker for Kidney Transplantation in Older Patients.

OBJECTIVE: Low skeletal muscle mass has emerged as a risk factor for mortality after liver transplantation. We evaluated the prognostic value of muscle mass on length of hospitalization and adverse outcomes after kidney transplantation in aging end-stage renal disease patients. METHODS: One hundred twenty-two patients aged 60 years or older at the time of transplantation were retrospectively analyzed. Skeletal muscle index (SMI), evaluated by computed tomography scan, was calculated from total muscle surface area at L3 vertebral level divided by body height squared. Outcomes were compared according to SMI (namely, length of hospitalization, wound complications, combined endpoint comprising all-cause mortality, and graft failure within 1 year). RESULTS: In male patients, by multivariate analysis, a low SMI (<42 cm2/m2) was associated with longer immediate post-transplantation hospitalization (ß = 17.03 ± 4.3; P = .0002), longer total hospitalization during the first year (ß = 34.3 ± 10.7; P = .002), higher rate of wound complications (odds ratio = 12.1 [1.9-77.0]; P = .008), and higher rate of the combined endpoint of graft loss or death (odds ratio = 3.4 [3.0-399.5]; P = .004). In female patients, low SMI was not associated with length of hospitalization or adverse outcomes after transplantation. CONCLUSION: SMI is an independent marker of morbidity and mortality after kidney transplantation in older men and could help thereby nephrologists better select aging candidates for kidney transplantation with a view to improving post-transplant outcomes.

Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, related to severe acute respiratory syndrome coronavirus 2 infection. Few data are available in patients with end-stage renal disease (ESRD). METHODS: We conducted an observational cohort study of COVID-19 patients at 11 dialysis centres in two distinct districts of France to examine the epidemiological and clinical characteristics of COVID-19 in this population, and to determine risk factors of disease severity (defined as a composite outcome including intensive care unit admission or death) and mortality. RESULTS: Among the 2336 patients enrolled, 5.5% had confirmed COVID-19 diagnosis. Of the 122 patients with a follow-up superior to 28 days, 37% reached the composite outcome and 28% died. Multivariate analysis showed that oxygen therapy on diagnosis and a decrease in lymphocyte count were independent risk factors associated with disease severity and with mortality. Chronic use of angiotensin II receptor blockers (ARBs) (18% of patients) was associated with a protective effect on mortality. Treatment with azithromycin and hydroxychloroquine (AZT/HCQ) (46% of patients) were not associated with the composite outcome and with death in univariate and multivariate analyses. CONCLUSIONS: COVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.

Homocitrulline as marker of protein carbamylation in hemodialyzed patients.

BACKGROUND: Homocitrulline (HCit) is a carbamylation-derived product (CDP) that has been identified as a valuable biomarker of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of this study was to determine whether initiation of hemodialysis therapy (HD) could induce variations of HCit concentrations in CKD patients. METHODS: Serum HCit concentrations were determined by LC-MS/MS in CKD patients (n=108) just before (M0) and six months (M6) after the initiation of HD therapy. RESULTS: Mean HCit concentrations reached 1000µmol/mol Lysine before initiation of HD therapy and decreased by 50% within 6months after HD onset. HCit concentrations remained stable over time as assessed during a 24-months follow-up period. HCit was mostly found in its protein-bound form in HD patients. HCit concentrations obtained at M0 were positively correlated with urea (r=0.58) and carbamylated hemoglobin (r=0.41), and are likely to be promising predictive markers of mortality. However, no correlations were found between HCit concentrations and Kt/V values, suggesting that HCit is not a marker of HD efficiency. CONCLUSION: HCit concentrations reflect the intensity of protein carbamylation and are stable over time during HD treatment, making HCit a reliable biomarker in the follow-up of CKD patients.

Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial.

BACKGROUND: Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly. METHODS: Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50-53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953. RESULTS: Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups. CONCLUSIONS: Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa.

[Why and how correct calcidiol deficiency in haemodialysis patients?]. / Pourquoi et comment corriger le déficit en calcidiol chez les patients hémodialysés ?

UNLABELLED: The plasma concentration of 25(OH) D - calcidiol - is low in most of stage 5 renal patients. Due to the lack of renal 1alpha-hydroxylase, no supplementation is recommended. However, calcidiol also displays many extraosseous beneficial antiproliferative effects. It may be useful to correct its deficiency in dialysis patients. The efficacy of an oral supplementation for 6 months with ergocalciferol, (Sterogyl), was evaluated in a monocentric cohort of 107 prevalent hemodialysis patients. Plasma levels of 25(OH) D, parathormone, total and ionized calcium, phosphates, were measured at month 0, 3 and 6 in all patients and plasma levels of 1-25(OH) D at month 0 and 6 in 38 patients with the lowest 25(OH) D levels at baseline. Patients were divided into four groups according to their initial 25(OH) D plasma levels and received ergocalciferol supplementation in accordance to the KDOQI Guidelines for stage 3 and 4 renal patients. RESULTS: 101/107 patients display low levels of 25(OH) D at baseline: mean 11.8+/-11.6 microg/l (normal> 30 microg/l). At the end of the initial three months correction period, the plasma levels of 25(OH) D rose significantly. However, only 60% of patients reach a normal plasma concentration of calcidiol with the highest - 600,000UI - ergocalciferol cumulative dosage. At the end of the three months maintenance period, plasma 25(OH) D concentrations fell in all patients. No significant change was observed in parathormone, calcium, phosphates and 1-25(OH) D plasma levels. There was no hypercalcemic episode. CONCLUSION: KDOQI ergocalciferol recommended doses for stages 3 and 4 renal patients did not correct calcidiol deficiency in hemodialysis patients. New prospective studies are required for defining the modalities of an efficient vitamin D supplementation with ergocalciferol or cholecalciferol.

The clinical evaluation of low-dose heparin in haemodialysis: a prospective study using the heparin-coated AN69 ST membrane.

BACKGROUND: The AN69 ST haemodialysis membrane, a new membrane resulting from coating polyethyleneimine upon the polyacrylonitrile surface, binds heparin. In patients at risk of bleeding, a pilot study has demonstrated the efficient anticoagulant effect of this heparin-coated membrane. Study design. In chronic haemodialyzed patients, we evaluated whether this anticoagulant effect can be validated in a controlled, prospective, open study. Pragmatically, we tested the hypothesis of no difference of the massive clotting rate in two groups of patients haemodialyzed either with 50% reduced standard doses of nonfractionated heparin using the heparin-coated AN69 ST or with a full dose of heparin (100%) using another type of dialysis membrane that does not bind heparin. Secondary objectives included evaluation of partial clotting, changes in haemoglobin levels, erythropoietin consumption and dialyzer performances. RESULTS: One hundred and eighty-four patients were elected and 170 finally included in an 18-month follow-up study. They were allocated to one of the two arms of the study. In the heparin-reduced group (n = 85, mean age: 73 +/- 11 years), 12 472 sessions were performed after priming the AN69 ST dialyzer with 2 L of heparinized saline (5000 IU/L heparin) and using 50% reduced doses of previously administered heparin. In the control group with standard heparin (n = 85, mean age: 74 +/- 13 years), 14 154 sessions were analysed (NS), and mean heparin doses were 2718 +/- 1388 and 4800 +/- 1564 IU per session, respectively (P < 0.001). In the heparin-reduced group, massive clotting occurred in 1.4 per 1000 sessions, whereas it occurred in 1.6 per 1000 sessions in the standard heparin group (P < 0.05). Mild to moderate partial clotting in the venous drip chamber and in the dialyzer was evaluated in a subset of patients, on a visual scale. It was more frequent in the experimental group than in the control group (P < 0.001). Platelets, haemoglobin levels, erythropoietin needs and dialyzer performances remained unchanged in both groups. The global mean death rate was 16.8% per year and did not differ significantly between groups. CONCLUSION: The use of the heparin-coated AN69 ST membrane allows a 50% reduction of standard doses of nonfractionated heparin administration for routine haemo- dialysis without increasing the risk of massive clotting of the extracorporeal circuit. This result needs confirmation since massive clotting questions clinical practice and is team dependent.